The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Endovascular thrombectomy for DAWN- and DEFUSE-3 ineligible acute ischemic stroke patients: a systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) has been proven beneficial for treating acute ischemic strokes (AIS) with large vessel occlusion (LVO). Recent trials of DAWN and DEFUSE-3 have extended the treatment window to 6-24 h, sparking investigations into EVT outcomes for patients not eligible for DAWN/DEFUSE-3 criteria. PURPOSE: To assess the outcomes of endovascular therapy (EVT) for late-window anterior circulation large vessel occlusion (LVO) in acute ischemic stroke patients, comparing DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) groups. METHODS: This systematic review and meta-analysis examined EVT outcomes for patients with late-window anterior circulation LVO beyond 6 h. We categorized patients as DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND). Our search covered PubMed, Embase, Web of Science, and Scopus. A total of 464 records were initially identified. After duplicate removal, 298 studies were screened. Nine studies were included and analyzed. Our analysis focused on study characteristics, baseline comparisons, risk of bias, and outcomes. RESULTS: Baseline characteristics showed comparable age, gender, most comorbidities, NIHSS score, and ASPECTS between DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) patients. NDND patients' history showed a higher rate of atrial fibrillation and larger infarct volumes on baseline imaging. Successful reperfusion rates (TICI 2b-3) were similar between DD and NDND with 354 out of 469 in the DD group and 364 out of 459 in the NDND group (OR = 0.86; 95% CI 0.40, 1.84; p = 0.689), though with significant heterogeneity (I2 = 73%; P = 0.002). The proportion of patients with distal occlusions was significantly higher in the NDND group as compared to the DD group (137 (39.4%) of 347 patients versus 47 (11%) of 428 patients, respectively), with significant heterogeneity across studies (I2 = 85%, p = 0.023). Functional independence at 90 days (mRS 0-2) showed no significant difference between groups with 259 out of 802 in the DD group and 197 out of 668 in the NDND group (OR = 1.12; 95% CI 0.77, 1.63; p = 0.552) but also exhibited notable heterogeneity (I2 = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rates were lower in DD with 14 out of 309 in the DD group and 47 out of 400 in NDND group (OR = 0.49; 95% CI 0.25, 0.93; p = 0.029) as compared to the NDND patients, showing no heterogeneity (I2 = 0%, p = 0.552). 90-day mortality was lower in DD with 43 out of 304 in the DD group and 107 out of 399 in the NDND group (OR = 0.55; 95% CI 0.37, 0.82; p = 0.004) as compared to NDND patients, with no significant heterogeneity (I2 = 0%, p = 0.536). CONCLUSION: This meta-analysis demonstrates equivalent rates of functional independence between DD and NDND patients. However, the high proportion of distal occlusions and higher rates of sICH and mortality in NDND patients suggest caution in offering mechanical thrombectomy to DAWN/DEFUSE-3 ineligible patients. A more flexible approach to EVT eligibility criteria could benefit select patients in real-world practice. Nonetheless, further research is needed to identify which patients would benefit from expanded EVT eligibility criteria.

Flow diverter stenting for intracranial aneurysms in the pediatric population: Two case reports and literature review.

The Pipeline Embolization Device (PED) is a flow-diverting intraluminal device that is approved for use in adults 18 years or older with internal carotid artery aneurysms. However, it can also be used off-label in pediatric patients with aneurysms that cannot be resolved with traditional endovascular treatments. Herein, we present two cases of flow diversion in the pediatric population with complete obliteration of the aneurysm and excellent outcomes. Flow diversion has been shown to be a safe endovascular option in treating complex aneurysms in children. Larger-sized, multicenter trials are encouraged to compare outcomes between flow diversion and other aneurysm treatment options given the rarity of pediatric aneurysms.

Effects of intravenous thrombolysis on stent retriever and aspiration thrombectomy outcomes: a systematic review and meta-analysis of the randomized controlled trials.

BACKGROUND: Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. METHODS: In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). RESULTS: Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. CONCLUSIONS: Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

Effect of Treatment Choice on Short-Term and Long-Term Outcomes for Carotid Near-Occlusion: A Meta-Analysis.

OBJECTIVE: Current guidelines recommend best medical treatment (BMT) over revascularization for carotid near-occlusion (CNO); however, it remains unclear whether BMT, carotid artery stenting (CAS), or carotid endarterectomy (CEA) is the optimal treatment strategy. The present meta-analysis aimed to compare outcomes among patients with CNO receiving BMT, CAS, or CEA. METHODS: PubMed, Web of Science, Scopus, and Embase were searched. English studies with ≥1 month follow-up, that used established CNO diagnostic guidelines, that provided outcomes by treatment, and in which 95% confidence intervals (CIs) were calculable were included. Studies on acute ischemic stroke (AIS) requiring emergent reperfusion therapy, nonatherosclerotic lesions, nonprimary research articles, non-English, and nonhuman studies were excluded. Outcomes were mortality, AIS, transient ischemic attack, myocardial infarction within and beyond 30 days, and restenosis. A generalized linear mixed model, subgroup analysis, and meta-regression were used to compare outcomes. RESULTS: Thirty-eight studies were included. Pooled rates for AIS beyond 30 days were 9.90% (95% CI, 4.31%-21.16%), 0.79% (95% CI, 0.24%-2.53%), and 0.80% (95% CI, 0.15%-4.07%) for BMT, CAS, and CEA, respectively. Subgroup analysis was statistically significant (P < 0.001). Meta-regression showed lower incidence favoring procedural intervention (CAS vs. BMT, P = 0.001; CEA vs. BMT, P = 0.003). Subgroup analysis for mortality beyond 30 days was also significant (P = 0.016) but meta-regression did not favor one treatment over another. Other outcomes were not statistically significant. CONCLUSIONS: Revascularization for CNO may decrease long-term stroke rates. Given that current guidelines are based on randomized controlled trials from the 1990s, updated randomized trials are warranted to determine the optimal treatment for CNO.

Aneurysmal recurrence and retreatment modalities after Woven EndoBridge (WEB) device implantation: A systematic review and meta-analysis.

BACKGROUND: The Woven EndoBridge (WEB) device is used to treat wide-neck bifurcation aneurysms (WNBAs). We conducted a systematic review and meta-analysis to determine the retreatment rate strategies following aneurysmal recurrence of WEB device treated WNBAs. METHODS: This study is reported following the PRISMA 2020 guidelines. We conducted a systematic review of the literature using PubMed, Scopus, Embase, and Web of Science. Data were pooled using a random-effects model. We calculated pooled prevalence and corresponding 95% confidence intervals (CI). RESULTS: We included 11 studies. The overall retreatment rate was 171/1875 aneurysms (10.3%; 95% CI = 8.3-12.9). Stent-assisted coiling was used to treat 59 aneurysms (36.7%; 95% CI = 26.4-48.5), and flow diverters were used to treat 44 aneurysms (18.7%; 95% CI = 9.9-32.5). Following retreatment, the complete occlusion rate was 57/91 aneurysms (62.8%; 95% CI = 48.2-75.3) and the adequate occlusion rate was 24/91 aneurysms (26.4%; 18.4%-36.4%). The most common aneurysmal recurrence site was the anterior communicating artery (44/136 aneurysms, 32.4%; 95% CI = 25.0-40.7). CONCLUSIONS: Roughly 10% of WNBAs initially treated with the WEB device will undergo retreatment. Retreatment is an effective strategy for WEB-treated aneurysms, with high rates of adequate and complete occlusion. Future studies should work to identify risk factors for aneurysmal recurrence.

CT Perfusion vs Noncontrast CT for Late Window Stroke Thrombectomy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) in the late window (6-24 hours) can be evaluated with CT perfusion (CTP) or with noncontrast CT (NCCT) only. Whether outcomes differ depending on the type of imaging selection is unknown. We conducted a systematic review and meta-analysis comparing outcomes between CTP and NCCT for EVT selection in the late therapeutic window. METHODS: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A systematic literature review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed databases. Studies focusing on late-window AIS undergoing EVT imaged through CTP and NCCT were included. Data were pooled using a random-effects model. The primary outcome of interest was rate of functional independence, defined as modified Rankin scale 0-2. The secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction 2b-3, mortality, and symptomatic intracranial hemorrhage (sICH). RESULTS: Five studies with 3,384 patients were included in our analysis. There were comparable rates of functional independence (odds ratio [OR] 1.03, 95% CI 0.87-1.22; p = 0.71) and sICH (OR 1.09, 95% CI 0.58-2.04; p = 0.80) between the 2 groups. Patients imaged with CTP had higher rates of successful reperfusion (OR 1.31, 95% CI 1.05-1.64; p = 0.015) and lower rates of mortality (OR 0.79, 95% CI 0.65-0.96; p = 0.017). DISCUSSION: Although recovery of functional independence after late-window EVT was not more common in patients selected by CTP when compared with patients selected by NCCT only, patients selected by CTP had lower mortality.

Stroke in Parkinson's disease: a review of epidemiological studies and potential pathophysiological mechanisms.

Parkinson's disease (PD) is the fastest growing neurological disorder and one of the leading neurological causes of disability worldwide following stroke. An overall aging global population, as well as general changes in lifestyle associated with mass industrialization in the last century, may be linked to both increased incidence rates of PD and an increase in cumulative cardiovascular risk. Recent epidemiological studies show an increased risk of stroke, post-stroke complications, and subclinical ischemic insults in PD. PD patients have a host of characteristics that might contribute to increasing the risk of developing ischemic stroke including motor impairment, dysautonomia, and sleep disorders. This increases the urgency to study the interplay between PD and other neurological disorders, and their combined effect on mortality, morbidity, and quality of life. In this review, we provide a comprehensive overview of the studied etiological factors and pathological processes involved in PD, specifically with regard to their relationship to stroke. We hope that this review offers an insight into the relationship between PD and ischemic stroke and motivates further studies in this regard.

Anti-seizure medications and efficacy against focal to bilateral tonic-clonic seizures: A systematic review with relevance for SUDEP prevention.

We conducted a systematic review of anti-seizure medications (ASMs) and their efficacy for the control of focal to bilateral tonic-clonic seizures (FBTCS). FBTCS, especially when nocturnal, are recognized as one of the major risk factors for Sudden Unexpected Death in Epilepsy (SUDEP). We searched different online databases for all the randomized, double-blinded, and placebo-controlled clinical trials of ASMs that were FDA-approved after 1990 and that reported specifically on the reduction in FBTCS; when possible, this was compared to reduction in focal impaired awareness (FIA) seizures. The ASMs that yielded the most data (3 or more studies) were topiramate (TPM), followed by tiagabine (TGB), brivaracetam (BRV), and lamotrigine (LTG). TPM trials showed a reduction in FBTCS of 44.8% to 100% (4.5-99% over placebo); TGB 21.8% to 46.7% (21.8-61% over placebo); BRV 33.9% to 82.1% (11.6-57.4% over placebo); and LTG 55.2% (20.3-52% over placebo). Promising results, but with data from only one or two studies, were seen with cenobamate (18-59% efficacy above placebo), lacosamide (45.1-78.7%), levetiracetam (40.1-60.3%), oxcarbazepine (58.5-81.5%), and gabapentin (50-53.8%). Higher responses were often seen at higher doses, including at doses above those currently approved by the FDA. Results specific to nocturnal FBTCS were never reported for any ASM. Moreover, complete freedom from FBTCS specifically was very rarely reported, despite its relevance for SUDEP prevention. In conclusion, there are few data specifically comparing the efficacy of ASMs for prevention of FBTCS despite the known strong association of BTCS with SUDEP. This review was our attempt at filling a gap in the literature and calling for universal reporting of data specific to BTC seizure reduction in all future studies, preferably including specific reporting on nocturnal BTCS. This will help enable rational ASM selection to minimize BTC seizures and thereby decrease the risk of SUDEP.

Development and validation of a predictive model of drug-resistant genetic generalized epilepsy.

OBJECTIVE: To develop and validate a clinical prediction model for antiepileptic drug (AED)-resistant genetic generalized epilepsy (GGE). METHOD: We performed a case-control study of patients with and without drug-resistant GGE, nested within ongoing longitudinal observational studies of AED response at 2 tertiary epilepsy centers. Using a validation dataset, we tested the predictive performance of 3 candidate models, developed from a training dataset. We then tested the candidate models' predictive ability on an external testing dataset. RESULTS: Of 5,189 patients in the ongoing longitudinal study, 121 met criteria for AED-resistant GGE and 468 met criteria for AED-responsive GGE. There were 66 patients with GGE in the external dataset, of whom 17 were cases. Catamenial epilepsy, history of a psychiatric condition, and seizure types were strongly related with drug-resistant GGE case status. Compared to women without catamenial epilepsy, women with catamenial epilepsy had about a fourfold increased risk for AED resistance. The calibration of 3 models, assessing the agreement between observed outcomes and predictions, was adequate. Discriminative ability, as measured with area under the receiver operating characteristic curve (AUC), ranged from 0.58 to 0.65. CONCLUSION: Catamenial epilepsy, history of a psychiatric condition, and the seizure type combination of generalized tonic clonic, myoclonic, and absence seizures are negative prognostic factors of drug-resistant GGE. The AUC of 0.6 is not consistent with truly effective separation of the groups, suggesting other unmeasured variables may need to be considered in future studies to improve predictability.